Semitransparent dark-red or ruby-red moisture- and air-sensitive single crystals of A(10+x)Ge(9)(2)W(1-x)Nb(x)O(4) (A = K, Rb; x = 0, 0.35) were obtained by high-temperature solid-state reactions. ...The crystal structure of the compounds was determined by single-crystal X-ray diffraction experiments. They crystallize in a new structure type (P2(1)/c, Z = 4) with a = 13.908(1) Å, b = 15.909(1) Å, c = 17.383(1) Å, and β = 90.050(6)° for K(10.35(1))Ge(9)(2)W(0.65(1))Nb(0.35(1))O(4); a = 14.361(3) Å, b = 16.356(3) Å, c = 17.839(4) Å, and β = 90.01(3)° for Rb(10.35(1))Ge(9)(2)W(0.65(1))Nb(0.35(1))O(4); a = 13.8979(2) Å, b = 15.5390(3) Å, c = 17.4007(3) Å, and β = 90.188(1)° for K(10)Ge(9)(2)WO(4); and a = 14.3230(7) Å, b = 15.9060(9) Å, c = 17.8634(9) Å, and β = 90.078(4)° for Rb(10)Ge(9)(2)WO(4). The compounds contain discrete Ge(9)(4-) Wade's nido clusters and WO(4)(2-) (or NbO(4)(3-)) anions, which are packed according to a hierarchical atom-to-cluster replacement of the Al(2)Cu prototype and are separated by K and Rb cations, respectively. The alkali metal atoms occupy the corresponding tetrahedral sites of the Al(2)Cu prototype. The amount of the alkali metal atoms on these diamagnetic compounds corresponds directly to the amount of W substituted by Nb. Thus, the transition metals W and Nb appear with oxidation numbers +6 and +5, respectively, in the vicinity of a Ge(9)(4-) polyanion. The crystals of the mixed salts were further characterized by Raman spectroscopy. The Raman data are in good agreement with the results from the X-ray structural analyses.
The endogenous 24‐h (circadian) rhythms exhibited by the cyanobacterium Synechococcus elongatus PCC 7942 and other organisms are entrained by a variety of environmental factors. In cyanobacteria, the ...mechanism that transduces environmental input signals to the central oscillator of the clock is not known. An earlier study identified ldpA as a gene involved in light‐dependent modulation of the circadian period, and a candidate member of a clock‐entraining input pathway. Here, we report that the LdpA protein is sensitive to the redox state of the cell and exhibits electron paramagnetic resonance spectra consistent with the presence of two Fe4S4 clusters. Moreover, LdpA copurifies with proteins previously shown to be integral parts of the circadian mechanism. We also demonstrate that LdpA affects both the absolute level and light‐dependent variation in abundance of CikA, a key input pathway component. The data suggest a novel input pathway to the circadian oscillator in which LdpA is a component of the clock protein complex that senses the redox state of a cell.
To examine the screening rates for kidney damage and function among patients with type 2 diabetes (T2D) and chronic kidney disease stage at diabetes diagnosis using a US administrative claims ...database.
This cohort study used a claims database enriched with laboratory results data. Patients with T2D (defined as 1 inpatient or 2 outpatient claims for diabetes), aged 18 years or older, and with at least 1 year of follow-up enrollment were identified. Patients with type 1 diabetes, kidney disease, or other related conditions at baseline were excluded. We estimated screening rates using laboratory orders for serum creatinine and estimated glomerular filtration rate (eGFR) measurement and urine albumin to creatinine ratio (UACR). Chronic kidney disease severity was reported using the Kidney Disease: Improving Global Outcomes classification based on laboratory results.
A total of 1,881,447 patients with T2D were eligible for analysis. Mean ± SD age was 63.1±13.1 years; 947,150 patients (50.3%) were male. Serum creatinine tests were ordered within 14 days of the index date among 290,722 patients of 622,915 (46.7%) patients with newly-recognized T2D. Overall, 1,595,964 patients (84.8%) had at least one serum creatinine test ordered during the 1-year follow-up period. Fewer patients received a UACR test during follow-up (814,897 43.3%). Less than half of all patients with T2D received a laboratory test order for both serum creatinine and urine albumin measurements during the follow-up period.
Physicians treating patients with diabetes are selectively adhering to chronic kidney disease screening guidelines, as indicated by high rates of eGFR testing, but less frequent UACR testing. Despite recommendations to monitor both eGFR and UACR, less than half of patients were screened for albuminuria during the 1-year follow-up.
Semitransparent dark-red or ruby-red moisture- and air-sensitive single crystals of A10+x Ge92W1–x Nb x O4 (A = K, Rb; x = 0, 0.35) were obtained by high-temperature solid-state reactions. The ...crystal structure of the compounds was determined by single-crystal X-ray diffraction experiments. They crystallize in a new structure type (P21 /c, Z = 4) with a = 13.908(1) Å, b = 15.909(1) Å, c = 17.383(1) Å, and β = 90.050(6)° for K10.35(1)Ge92W0.65(1)Nb0.35(1)O4; a = 14.361(3) Å, b = 16.356(3) Å, c = 17.839(4) Å, and β = 90.01(3)° for Rb10.35(1)Ge92W0.65(1)Nb0.35(1)O4; a = 13.8979(2) Å, b = 15.5390(3) Å, c = 17.4007(3) Å, and β = 90.188(1)° for K10Ge92WO4; and a = 14.3230(7) Å, b = 15.9060(9) Å, c = 17.8634(9) Å, and β = 90.078(4)° for Rb10Ge92WO4. The compounds contain discrete Ge9 4– Wade’s nido clusters and WO4 2– (or NbO4 3–) anions, which are packed according to a hierarchical atom-to-cluster replacement of the Al2Cu prototype and are separated by K and Rb cations, respectively. The alkali metal atoms occupy the corresponding tetrahedral sites of the Al2Cu prototype. The amount of the alkali metal atoms on these diamagnetic compounds corresponds directly to the amount of W substituted by Nb. Thus, the transition metals W and Nb appear with oxidation numbers +6 and +5, respectively, in the vicinity of a Ge94– polyanion. The crystals of the mixed salts were further characterized by Raman spectroscopy. The Raman data are in good agreement with the results from the X-ray structural analyses.
Organic Solid-Solid Wetting Deposition (OSWD) enables the fabrication of supramolecular architectures without the need for solubility or vacuum conditions. The technique is based on a process which ...directly generates two-dimensional monolayers from three-dimensional solid organic powders. Consequently, insoluble organic pigments and semiconductors can be made to induce monolayer self-assembly on substrate surfaces, such as graphene and carbon nanotubes, under ambient conditions. The above factuality hence opens up the potential of the OSWD for bandgap engineering applications within the context of carbon based nanoelectronics. However, the doping of graphene via OSWD has not yet been verified, primarily owing to the fact that the classical OSWD preparation procedures do not allow for the analysis via Raman spectroscopy, one of the main techniques to determine graphene doping. Hence, here we describe a novel approach to induce OSWD on graphene leading to samples suitable for Raman spectroscopy. The analysis reveals peak shifts within the Raman spectrum of graphene, which are characteristics for p-type doping. Additional evidence for chemical doping is found via Scanning Tunneling Spectroscopy. The results open up a very easily applicable, low-cost, and eco-friendly way for doping graphene via commercially available organic pigments.
The NTnC genetically encoded calcium indicator has an advantageous design because of its smaller size, GFP-like N- and C-terminal ends and two-fold reduced number of calcium binding sites compared ...with widely used indicators from the GCaMP family. However, NTnC has an inverted and modest calcium response and a low temporal resolution. By replacing the mNeonGreen fluorescent part in NTnC with EYFP, we engineered an NTnC-like indicator, referred to as YTnC, that had a positive and substantially improved calcium response and faster kinetics. YTnC had a 3-fold higher calcium response and 13.6-fold lower brightness than NTnC in vitro. According to stopped-flow experiments performed in vitro, YTnC had 4-fold faster calcium-dissociation kinetics than NTnC. In HeLa cells, YTnC exhibited a 3.3-fold lower brightness and 4.9-fold increased response to calcium transients than NTnC. The spontaneous activity of neuronal cultures induced a 3.6-fold larger ΔF/F response of YTnC than previously shown for NTnC. On patched neurons, YTnC had a 2.6-fold lower ΔF/F than GCaMP6s. YTnC successfully visualized calcium transients in neurons in the cortex of anesthetized mice and the hippocampus of awake mice using single- and two-photon microscopy. Moreover, YTnC outperformed GCaMP6s in the mitochondria and endoplasmic reticulum of cultured HeLa and neuronal cells.
Chronic kidney disease (CKD) is one of the most common complications of type 2 diabetes mellitus (T2D) and results in considerable economic burden. Current studies describing cost and health care ...resource utilization (HCRU) in T2D patients with CKD in real-world data are few. Even more scarce is evidence that takes into account disease severity and other comorbidities.
To (a) describe T2D patients with CKD identified in U.S. administrative claims data using laboratory test results for kidney function that are considered the gold standard criteria for kidney disease diagnosis and (b) estimate the annual HCRU and costs among these patients, overall and by disease severity and comorbidity subgroup.
Optum CDM data between the years 2008 and 2017 were used to identify T2D patients with newly recognized CKD, using laboratory test results for estimated glomerular filtration rate (eGFR) or urine albumin-to-creatinine ratio (UACR). The study estimated annualized total, inpatient, outpatient, and pharmacy costs and the number of outpatient, inpatient, and emergency room visits in the first year after CKD identification. Analyses were stratified by prevalent anemia, heart failure (HF), resistant hypertension, and by CKD stages.
T2D patients with newly recognized CKD (n = 106,369) had a high prevalence of cardiovascular comorbidities and incurred on average $24,029 of total cost per person per year in the first year after CKD identification. Patients with HF and anemia incurred on average $41,951 and $31,127 of total annual cost, respectively. Patients identified at stage 5 CKD incurred on average $110,210 of total annual cost and had roughly a 7-fold higher annual inpatient hospitalization rate compared with patients identified at stage 1 CKD.
Administrative claims data linked to laboratory results provide an opportunity to identify CKD patients using the gold standard criteria from clinical practice, minimizing potential misclassification of patients. Identified CKD patients, particularly those with HF, anemia, and more advanced CKD stage, incur high HCRU and cost. Better monitoring, earlier CKD diagnosis, and interventions that are effective in halting or slowing the progression of CKD, as well as at managing comorbid conditions, could be effective means to reduce the economic burden of CKD in T2D.
This study was funded by Bayer. Kelly is an employee of, and owns stock options in, Aetion, which was contracted by Bayer to conduct the study. Petruski-Ivleva was an employee of Aetion during the planning, analysis, and interpretation stages of the study. Kovesdy received honoraria from Amgen, Astra Zeneca, Bayer, Cara Therapeutics, Reata, Takeda, and Tricida. Fried received consultant fees from Bayer, Novo Nordisk, and Bristol-Meyers Squibb. Folkerts, Blankenburg, and Gay are Bayer employees. This work was presented as a poster at the annual European Association for the Study of Diabetes (EASD) conference held in Barcelona, Spain, on September 16-20, 2019.
Many patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) experience a delay in treatment or fail to initiate treatment with guideline-recommended angiotensin-converting enzyme ...inhibitors (ACEis) or angiotensin receptor blockers (ARBs) after CKD diagnosis. This study aimed to describe treatment patterns and treatment initiation after initial CKD diagnosis among patients with T2D.
Retrospective analysis using data from the Optum Clinformatics Data Mart administrative claims database (January 2014-September 2018).
Adult patients with T2D entered the cohort if they met the criteria for CKD, defined as 2 laboratory test results 90 to 365 days apart (January 2014-September 2017) indicating CKD. Included were patients with no prior use of ACEis or ARBs or evidence of kidney disease in the 365 days prior to cohort entry (baseline). Patients were followed for a maximum of 365 days and were censored on death, disenrollment, or end of data. Patient demographics, comorbidities, and medication use were assessed at baseline, and treatments were assessed over a 1-year followup period. Multivariate logistic regression was used to identify factors associated with ACEi or ARB initiation.
Among 15,400 eligible patients without prior ACEi or ARB treatment, only 17% initiated such therapy within a year after meeting CKD criteria. Patients who were White, resided in the northeastern United States, had more comorbidities, had less advanced albuminuria, or used sodium-glucose cotransporter 2 inhibitors were less likely to initiate treatment.
A large proportion of patients with T2D meeting criteria for CKD do not initiate the recommended therapy within 1 year of CKD diagnosis, highlighting a need for new therapies that can slow the progression of CKD.
ABSTRACT
Background
Chronic kidney disease (CKD), one of the most common complications of type 2 diabetes (T2D), is associated with poor health outcomes and high healthcare expenditures. As the CKD ...population increases, a better understanding of the prevalence and progression of CKD is critical. However, few contemporary studies have explored the progression of CKD relative to its onset in T2D patients using established markers derived from real-world care settings.
Methods
This retrospective, population-based cohort study assessed CKD progression among adults with T2D and with newly recognized CKD identified from US administrative claims data between 1 January 2008 and 30 September 2018. Included were patients with T2D and laboratory evidence of CKD as indicated by the established estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) criteria. Disease progression was described as transitions across the eGFR- and UACR-based stages.
Results
A total of 65 731 and 23 035 patients with T2D contributed to the analysis of eGFR- and UACR-based CKD stage progression, respectively. CKD worsening was observed in approximately 10–17% of patients over a median follow-up of 2 years. Approximately one-third of patients experienced an increase in eGFR values or a decrease in UACR values during follow-up.
Conclusions
A relatively high proportion of patients were observed with disease progression over a short period of time, highlighting the need for better identification of patients at risk of rapidly progressive CKD. Future studies are needed to determine the clinical characteristics of these patients to inform earlier diagnostic and therapeutic interventions aimed at slowing disease progression.
Graphical Abstract
CKD, a common complication of type-2 diabetes (T2D), causes considerable disease burden. Patients with T2D and CKD are considered high-risk for complications; however, studies describing patients ...with T2D and incident CKD identified from real-world data using the diagnostic gold-standard criteria - estimated glomerular filtration rate and urine albumin-to-creatinine ratio (UACR) - are scarce.
In this population-based cohort study, we sought to estimate the rates of cardiovascular and renal outcomes among patients with T2D and CKD by comorbidity subgroups and CKD severity. Patients were sampled between 2008 and 2017 from de-identified US administrative claims enriched with laboratory data. Analyses were stratified by prevalent heart failure (HF), anemia, and resistant hypertension and the KDIGO categories at index.
We identified 106,369 patients with T2D and incident CKD. The rate of all-cause hospitalization was 189 95% CI: 187, 191 per 1,000 person-years with cardiovascular-related hospitalizations being more frequent than kidney-related outcomes. The rate of acute kidney failure was 77.3 95% CI: 76.2, 78.5 per 1,000 person-years. Patients with HF experienced a 4-times higher rate for cardiovascular events compared to those without. Rates of hospitalization increased from 5- to 6-fold with increasing KDIGO severity.
Multimorbidity and advance stages of CKD increase the risk of cardiovascular and renal complications among patients with T2D diabetes. Earlier CKD diagnosis as well as interventions and coordinated care addressing other comorbid conditions present at diagnosis may reduce the overall disease burden in this population.
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